Normoxic cardiopulmonary bypass reduces oxidative myocardial damage and nitric oxide during cardiac operations in the adult

AbstractObjective: Hyperoxic cardiopulmonary bypass is widely used during cardiac operations in the adult. This management may cause oxygenation injury induced by oxygen-derived free radicals and nitric oxide. Oxidative damage may be significantly limited by maintaining a more physiologic oxygen tension strategy (normoxic cardiopulmonary bypass). Methods: During elective coronary artery bypass grafting, 40 consecutive patients underwent either hyperoxic (oxygen tension = 400 mm Hg) or normoxic (oxygen tension = 140 mm Hg) cardiopulmonary bypass. At the beginning and the end of bypass this study assessed polymorphonuclear leukocyte elastase, nitrate, creatine kinase, and lactic dehydrogenase, antioxidant levels, and malondialdehyde in coronary sinus blood. Cardiac index was measured before and after cardiopulmonary bypass. Results: There was no difference between groups with regard to age, sex, severity of disease, ejection fraction, number of grafts, duration of cardiopulmonary bypass, or ischemic time. Hyperoxic bypass resulted in higher levels of polymorphonuclear leukocyte elastase (377 ± 34 vs 171 ± 32 ng/ml, p = 0.0001), creatine kinase 672 ± 130 vs 293 ± 21 U/L, p = 0.002), lactic dehydrogenase (553 ± 48 vs 301 ± 12 U/L, p = 0.003), antioxidants (1.97 ± 0.10 vs 1.41 ± 0.11 mmol/L, p = 0.01), malondialdehyde (1.36 ± 0.1 μmol/L, p = 0.005), and nitrate (19.3 ± 2.9 vs 10.1 ± 2.1 μmol/L, p = 0.002), as well as reduction in lung vital capacity (66% ± 2% vs 81% ± 1%, p = 0.01) and forced 1-second expiratory volume (63% ± 10% vs 93% ± 4%, p = 0.005) compared with normoxic management. Cardiac index after cardiopulmonary bypass at low filling pressure was similar between groups (3.1 ± 0.2 vs 3.3 ± 0.3 L/min per square meter). [Data are mean ± standard error (analysis of variance), with p values compared with an oxygen tension of 400 mm Hg. Conclusions: Hyperoxic cardiopulmonary bypass during cardiac operations in adults results in oxidative myocardial damage related to oxygen-derived free radicals and nitric oxide. These adverse effects can be markedly limited by reduced oxygen tension management. The concept of normoxic cardiopulmonary bypass may be applied to surgical advantage during cardiac operations. (J Thorac Cardiovasc Surg 1998;116:327-34

High colloid oncotic pressure priming of cardiopulmonary bypass in neonates and infants: implications on haemofiltration, weight gain and renal function

Abstract Objective: To evaluate the influence of high colloid oncotic pressure (COP) priming of cardiopulmonary bypass (CPB) on fluid balances, haemofiltration, capillary leakage and renal function in neonates and infants. Methods: Twenty neonates or infants underwent heart surgery using CPB and were randomised in two groups. For group 1 (FFP-group) a blood priming with fresh frozen plasma (FFP, low oncotic pressure) was chosen, for group 2 (HA-group) a blood priming containing FFP and human albumin 20% (HA) to realise higher oncotic pressures was substituted. All patients were monitored before, during and 6 h after CPB. We measured weights, fluid balances, transfusion volumes, colloid oncotic pressures, inflammatory parameters (c-reactive protein, interleukin-6, interleukin-8, thrombocytes, leucocytes) and renal function (creatinine clearances, renal protein losses). Results: Patient's demographics and operational procedures were comparable in both groups with no further differences in operation procedures regarding palliation or correction. Colloid oncotic pressures of the priming solutions were higher in the HA-group (28 mmHg AE 4.9) than in the FFP-group (6 mmHg AE 1.3, p < 0.001). Relative weight gain as a marker of capillary leakage in the HA-group (2% AE 4.5) was significantly lower 6 h post CPB than in the FFP-group (8% AE 8.0, p = 0.015). Haemofiltration rates were higher in the HA-group (569 ml AE 197 vs 282 ml AE 157, p = 0.002) on CPB. There were no differences of creatinine clearances 6 h after the end of CPB. Renal protein losses were elevated in both groups without any inter-group differences during and 6 h after CPB. Conclusion: Addition of concentrated human albumin to priming fluids in paediatric cardiac surgery leads to less weight gain even after CPB. Supplementing paediatric patients undergoing cardiac surgery with concentrated human albumin does not affect renal function more severely than in paediatric patients undergoing cardiac surgery on CPB with blood priming.

Multidirectional flow analysis by cardiovascular magnetic resonance in aneurysm development following repair of aortic coarctation

Aneurysm formation is a life-threatening complication after operative therapy in coarctation. The identification of patients at risk for the development of such secondary pathologies is of high interest and requires a detailed understanding of the link between vascular malformation and altered hemodynamics. The routine morphometric follow-up by magnetic resonance angiography is a well-established technique. However, the intrinsic sensitivity of magnetic resonance (MR) towards motion offers the possibility to additionally investigate hemodynamic consequences of morphological changes of the aorta

Clinical experience with the ATS 3f Enable® Sutureless Bioprosthesis

Objective: The ATS 3f Enable® Bioprosthesis is a self-expanding valve with a tubular design that allows for decreased leaflet stress and preservation of aortic sinuses. We report the midterm results of a prospective, multicenter clinical study evaluating the safety and efficacy of this stented bioprosthesis in patients undergoing isolated aortic valve replacement with or without concomitant procedures. Methods: A total of 140 patients (mean age: 76±6years; 63% of patients in New York Heart Association (NYHA) stage III-IV) received the ATS 3f Enable® Bioprosthesis in 10 European centers between March 2007 and December 2009. The total accumulated follow-up is 121.8 patient-years. Results: Valve implantation resulted in significant improvement of patients' symptoms. Mean systolic gradient was 9.04±3.56 and 8.62±3.16mmHg with mean effective orifice area of 1.69±0.52 and 1.67±0.44 at 6 months and 1 year, respectively. No significant transvalvular aortic regurgitation was observed. Early complications included three major paravalvular leaks (PVL; 2.1%) resulting in valve explantation and one thrombo-embolic (0.7%) event. All, but one, of the early PVLs were evident intra-operatively with the medical decision made not to reposition or resolve immediately. Late adverse events included three explantations (2.5% per patient-year): one due to PVL and two due to endocarditis. There was an additional case of late endocarditis (0.8% per patient-year) that resolved by medical management. No structural deterioration, valve-related thrombosis or hemolysis was documented. Conclusions: The sutureless valve implantation technique is feasible and safe with the ATS 3f Enable Bioprosthesis. Valve implantation resulted in excellent hemodynamics and significant clinical improvement. Overall, these data confirm the safety and clinical utility of the Enable® Bioprosthesis for aortic valve replacemen

Long-Term Follow-Up of Survivors of Extracorporeal Life Support Therapy for Cardiogenic Shock: Are They Really Survivors?

Background and Objectives: Cardiogenic shock (CS) is a medical emergency associated with a high mortality rate. Veno-arterial extracorporeal membrane oxygenation (VA-ECMO) has become an accepted therapy for CS. Despite widely available data for short-term survival rates, there are only limited data available regarding long-term outcomes following successful VA-ECMO therapy. Materials and Methods: We analyzed the demographics, past medical history, adverse events, and outcomes of survivors who received VA-ECMO support for CS at our center from January 2012 to December 2019. Post-cardiotomy cases were excluded. Results: A total of 578 VA-ECMO implantations on 564 consecutive patients due to CS were identified during the study period. Successful weaning was achieved in 207 (36.7%) patients. Among the survivors, 126 (63%) patients received VA-ECMO therapy without preceding cardiac surgery during their current admission. A follow-up exceeding 12 (mean: 36 ± 20.9) months was available in a total of 55 (43.7%) survivors. The mean VA-ECMO perfusion time was 10.9 (±7.7) days with a mean intensive care unit (ICU) stay of 38.2 (±29.9) days and a mean hospital stay of 49.9 (±30.5) days. A total of 3 deaths were recorded during long-term follow-up (mean survival of 26 ± 5.3 months). Conclusions: Despite the high mortality associated with VA-ECMO therapy, a long-term follow-up with an acceptably low rate of negative cardiac events can be achieved in many survivors. We observed an acceptable low rate of new cardiac events. Further evaluation, including a quality-of-life assessment and a close follow-up for rarer complications in these patients, is needed to elucidate the longer-term outcomes for survivors of invasive VA-ECMO therapy

Experimental Evaluation of Gene Silencing As New Therapeutic Option in the Treatment of Gemcitabine-chemoresistant Non-small-cell Lung Cancer

The evolution of technological and therapeutic applications of siRNA since the description of the interference process in 2006 has been extremely rapid and very productive. Currently, at least ten tumor entities and ten viral infections in which siRNA-based therapy might play an auspicious role have been described. Because of the very poor prognosis of NSCLC, we examined and proposed a new therapeutic alternative for the treatment of gemcitabine-resistant lung cancer via siRNA-specific silencing of six important molecules involved in lung carcinogenesis.Methods: One hundred thousand gemcitabine-chemoresistant A549 cell lines were cultured in a humidified atmosphere containing 5 % CO2 at 37°C and were transfected with specific siRNA targeting HIF1, HIF2, STAT3, SRF, E2F1 and Survivin. The relative expression of these molecules was examined via qRT-PCR and the viability of the chemoresistant cells after siRNA transfection was analyzed using a CASY system 72 hours after specific transfection.Results: The relative expression of the examined target molecules was suppressed by up to 73 % after specific transfection, and the CASY system demonstrated a concentration-dependent reduction in the viability of chemoresistant A549 cells of up to 61 %. Therefore the obtained results were significantly better in comparison to the control group.Conclusions: siRNA complexes may induce accurate suppression of various target molecules involved in lung tumor growth, in particular in gemcitabine- chemoresistant adenocarcinoma. Therefore, siRNA-based nanotechnology might represent a productive platform for the development of new chemotherapeutic agents for advanced stages of lung cancer in the context of a personalized multimodality regimen

Cell-Wall Glycolipid Mutations and Their Effects on Virulence of E. faecalis in a Rat Model of Infective Endocarditis

Enterococci are among the major pathogens implicated in cardiac infections and biofilm formation. E. faecalis has been shown to play an important role in infectious endocarditis. Several distinct mechanisms for biofilm formation have been identified in E. faecalis. Our group has previously characterized two distinct bacterial glucosyltransferases playing key roles in the production of the major cell wall glycolipids and leading to reduced biofilm production. To assess if this mechanism is involved in the pathogenesis of enterococcal endocarditis we compared the wild-type strain of E. faecalis 12030 with two mutants in gene EF2891 and EF2890 respectively in a rat model of infective endocarditis. The results showed less endocarditic lesions and reduced colony counts per vegetation in the two mutants. indicating that the modification of bacterial surface lipids results in significantly reduced virulence in infective endocarditis. These results underscore the important role of biofilm formation in the pathogenicity of enterococcal endocarditis and may indicate an interesting target for novel therapeutic strategies

Penetration of left and right atrial wall and aortic root by an Amplatzer atrial septal occluder in a nine year old boy with Marfan syndrome: Case report

<p>Abstract</p> <p>Background</p> <p>To describe complications associated with Amplatzer septal occluders in a patient with Marfan syndrome</p> <p>Case presentation</p> <p>A nine-year-old boy with Marfan syndrome and a 22 mm atrial septal defect (ASD) was treated successfully by interventional closure of his ASD by placing a 24 mm Amplatzer septal occluder. Follow up examinations showed a good result but an increasing enlargement of aortic root, so the patient was scheduled for operation. Intraoperative findings showed a perforation of the left atrial roof and the non-coronary sinus by penetration of the occluder device as well as penetration into the right atrial wall. The occluder was resected, the ASD was closed and the aortic sinus was reconstructed using a Dacron patch.</p> <p>Conclusion</p> <p>We describe the first case of a patient with Marfan syndrome and an interventional closure of an ASD. Due to alterations of the connective tissue, as it is typical for patients with Marfan syndrome, the Amplatzer occluder probably perforated adjacent structures more easily as in non-affected individuals. Amplatzer occluders should be used with caution and follow up examinations should be performed in short intervals.</p

Chylothorax after surgery on congenital heart disease in newborns and infants -risk factors and efficacy of MCT-diet

<p>Abstract</p> <p>Objectives</p> <p>To analyze risk factors for chylothorax in infants after congenital heart surgery and the efficacy of median chain triglyceride diet (MCT). To develop our therapeutic pathway for the management of chylothorax.</p> <p>Patients and methods</p> <p>Retrospective review of the institutional surgical database and patient charts including detailed perioperative informations between 1/2000 and 10/2006. Data analyzing with an elimination regression analysis.</p> <p>Results</p> <p>Twenty six out of 282 patients had chylothorax (=9.2%). Secondary chest closure, low body weight, small size, longer cardiopulmonary bypass (242 ± 30 versus 129 ± 5 min) and x-clamp times (111 ± 15 versus 62 ± 3 min) were significantly associated with chylothorax (p < 0.05). One patient was cured with total parenteral nutrition (TPN) and one without any treatment. 24 patients received MCT-diet alone, which was successful in 17 patients within 10 days. After conversion to regular alimentation within one week only one chylothorax relapsed. Out of 7 patients primarily not responsive to MCT-diet, 2 were successfully treated by lysis of a caval vein thrombosis, 2 by TPN + pleurodesis + supradiaphragmatic thoracic duct ligation, one by octreotide treatment, and two patients finally died.</p> <p>Conclusions</p> <p>Chylothorax may appear due to injury of the thoracic duct, due to venous or lymphatic congestion, central vein thrombosis, or diffuse injury of mediastinal lymphatic tissue in association with secondary chest closure. Application of MCT alone was effective in 71%, and more invasive treatments like TPN should not be used in primary routine. After resolution of chylothorax, MCT-diet can be converted to regular milk formula within one week and with very low risk of relapse.</p